Bioinspired Total Synthesis of Hyperireflexolides A and B

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Biosynthesis

Background:

• Hyperireflexolides A and B are complex natural products.
• Their proposed biosynthetic pathway involves significant molecular rearrangement.
• Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of natural products with diverse biological activities.

Purpose of the Study:

• To synthesize hyperireflexolides A and B.
• To validate the proposed biosynthetic pathway for hyperireflexolides.
• To explore novel synthetic strategies for complex PPAPs.

Main Methods:

• Total synthesis of hyperireflexolides A and B in six steps.
• Utilized dearomatization and fragmentation of an acylphloroglucinol starting material.
• Employed oxidative radical cyclization, retro-Dieckmann fragmentation, and stereodivergent carbonyl-ene reactions.

Main Results:

• Successful synthesis of hyperireflexolides A and B.
• Demonstrated the feasibility of the proposed biosynthetic route.
• The synthetic sequence included α-hydroxy-β-diketone rearrangements.

Conclusions:

• The total synthesis provides strong support for the proposed biosynthetic pathway of hyperireflexolides.
• The structural revision of hyperireflexolide B is consistent with the synthetic findings.
• This work offers a new synthetic strategy for accessing highly rearranged PPAPs.